The emerging role of Lactobacillus acidophilus in the cervicovaginal microenvironment
Authors: Mariano A Molina, Willem J G Melchers, Virginia Núñez-Samudio, Iván Landires
Journal: The Lancet Microbe (2023)

Lactobacillus acidophilus is a Gram-positive, rod-shaped bacterium commonly found in several body sites including the gut and female genital tracts. L acidophilus can ferment sugars to produce lactic acid, which helps create an acidic environment that inhibits the growth of harmful bacteria and promotes the growth of beneficial bacteria. As a probiotic, L acidophilus has been shown to help mitigate symptoms of irritable bowel syndrome in adults and improve dysentery in children.1Rousseaux C Thuru X Gelot A et al.Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors.Nat Med. 2007; 13: 35-37Crossref PubMed Scopus (649) Google Scholar, 2Łukasik J Dierikx T Besseling-van der Vaart I et al.Multispecies probiotic for the prevention of antibiotic-associated diarrhea in children: a randomized clinical trial.JAMA Pediatr. 2022; 176: 860-866Crossref PubMed Scopus (12) Google Scholar Hence, L acidophilus is thought to have a crucial role in maintaining healthy microbiomes and supporting human health. Studies from the past 3 years have also highlighted its role in the cervicovaginal microbiome (CVM) with substantial implications for women's health. The CVM is a complex microbial ecosystem that varies widely between women and ethnicities, and over time.3Ravel J Gajer P Abdo Z et al.Vaginal microbiome of reproductive-age women.Proc Natl Acad Sci USA. 2011; 108: 4680-4687Crossref PubMed Scopus (2553) Google Scholar The dominant paradigm has been that cervicovaginal communities are either dominated by Lactobacillus species or have a highly diverse composition. These community state types (CSTs) are generally abundant in L crispatus, L gasseri, L iners, L jensenii, and Gardnerella vaginalis.3Ravel J Gajer P Abdo Z et al.Vaginal microbiome of reproductive-age women.Proc Natl Acad Sci USA. 2011; 108: 4680-4687Crossref PubMed Scopus (2553) Google Scholar Studies from 2022 and 2023, however, have challenged this paradigm by proposing that the CVM has a continuous composition.4Lebeer S Ahannach S Wittouck S et al.Citizen-science map of the vaginal microbiome.Res Sq. 2022; (published online Feb 14.) (preprint).https://doi.org/10.21203/rs.3.rs-1350465/v1Google Scholar, 5Lee CY Dillard LR Papin JA Arnold KB New perspectives into the vaginal microbiome with systems biology.Trends Microbiol. 2023; 31: 356-368Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar This concept suggests that instead of separate microbial communities, there is a spectrum of CSTs present in the microenvironment, ranging from those dominated by Lactobacillus species to those that are more diverse and less beneficial to health. In this context, L acidophilus has emerged as an important species associated with the dynamics occurring between CSTs that could, therefore, have a role in the continuity of the CVM.6Molina MA Andralojc KM Huynen MA Leenders WPJ Melchers WJG In-depth insights into cervicovaginal microbial communities and hrHPV infections using high-resolution microbiome profiling.NPJ Biofilms Microbiomes. 2022; 8: 75Crossref PubMed Scopus (3) Google Scholar The identification of L acidophilus in the CVM has been a challenge in previous microbiome studies because the bacterium is closely related to other Lactobacillus species. Advances in sequencing technologies, bioinformatics tools, and primer design have supported deeper analyses into CVM composition.6Molina MA Andralojc KM Huynen MA Leenders WPJ Melchers WJG In-depth insights into cervicovaginal microbial communities and hrHPV infections using high-resolution microbiome profiling.NPJ Biofilms Microbiomes. 2022; 8: 75Crossref PubMed Scopus (3) Google Scholar Flaviani and colleagues7Flaviani F Hezelgrave NL Kanno T et al.Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort.JCI Insight. 2021; 6e149257 Crossref PubMed Scopus (28) Google Scholar explored the associations between the cervicovaginal microbiota and pregnancy in a prospective longitudinal cohort of pregnant women in the UK in 2021. They reported that L acidophilus had a protective and predictive role for spontaneous preterm birth and recommended its use as a probiotic supplement.7Flaviani F Hezelgrave NL Kanno T et al.Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort.JCI Insight. 2021; 6e149257 Crossref PubMed Scopus (28) Google Scholar Similarly, Pacha-Herrera and colleagues8Pacha-Herrera D Erazo-Garcia MP Cueva DF et al.Clustering analysis of the multi-microbial consortium by Lactobacillus species against vaginal dysbiosis among Ecuadorian women.Front Cell Infect Microbiol. 2022; 12863208 Crossref PubMed Scopus (15) Google Scholar observed in 2022 that L acidophilus was present in the CVMs of 28% of the Ecuadorian women included in their study and associated the species with protection against bacterial vaginosis. These findings suggest that L acidophilus has a key role in maintaining vaginal health and preventing adverse outcomes. L acidophilus has also emerged in the context of high-risk human papillomavirus (hrHPV) infections.9Andralojc KM Molina MA Qiu M et al.Novel high-resolution targeted sequencing of the cervicovaginal microbiome.BMC Biol. 2021; 19: 267Crossref PubMed Scopus (8) Google Scholar HPV is a common sexually transmitted infection that can lead to cervical cancer. It is estimated that up to 80% of all sexually active women will be infected with hrHPV at some point in their lives. The disease burden of cervical cancer has been reduced due to HPV vaccination, but the circulation of non-vaccine-preventable HPV types presents a risk for global HPV vaccination programmes. Nevertheless, not all women who are infected with hrHPV will develop cervical cancer, and researchers are increasingly interested in understanding why. One possible explanation is that beneficial bacteria in the CVM, such as L acidophilus, might help protect against the development of cervical cancer in women who are infected with hrHPV. By applying high-resolution microbiome profiling, Andralojc and colleagues9Andralojc KM Molina MA Qiu M et al.Novel high-resolution targeted sequencing of the cervicovaginal microbiome.BMC Biol. 2021; 19: 267Crossref PubMed Scopus (8) Google Scholar clinically assessed these associations in women participating in the Dutch cervical cancer screening programme. In a cross-sectional study comparing hrHPV-negative cervical smears without abnormalities with hrHPV-positive cervical smears with high-grade intraepithelial neoplasia, they found that women with typical cervical smears had a higher abundance of L acidophilus in their CVMs than women with cervical smears with high-grade intraepithelial neoplasia.9Andralojc KM Molina MA Qiu M et al.Novel high-resolution targeted sequencing of the cervicovaginal microbiome.BMC Biol. 2021; 19: 267Crossref PubMed Scopus (8) Google Scholar Further analyses allowed them to define new cervicovaginal microbial communities and microbiome dynamics on the basis of the abundance of L acidophilus,10Molina MA Melchers WJG Andralojc KM Leenders WPJ Huynen MA Longitudinal analysis on the ecological dynamics of the cervicovaginal microbiome in hrHPV infection.Comput Struct Biotechnol J. 2023; 21: 4424-4431Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar all of which support the continuity of the CVM. Although more research is needed to fully understand the role of L acidophilus in cervical health, hrHPV infections, and cervical cancer, these findings suggest that this bacterium could have an important role in the CVM, highlighting the need for further research into the complex interactions between Lactobacillus and other bacterial species and the potential implications for disease outcomes and therapies. As our understanding of the CVM continues to evolve, we will probably discover more about how L acidophilus and other species have a role in women's health. We declare no competing interests.